BRCA 1 and 2: the genes, the myths, the mutations

You've probably heard about the genes, BRCA 1 and 2 - most likely when Angelina Jolie's double mastectomy hit the headlines in May this year - or maybe more generally, in relation to risk of breast or ovarian cancer in women. Perhaps you've also heard about BRCA 1 and 2 in relation to prostate cancer, and the world's first preventative prostatectomy that wasn't?

But what are the BRCA genes? Why is it such a problem when they change or 'mutate'? And, what does a BRCA gene mutation mean for men? 

What are the BRCA genes?

BRCA1 and BRCA2 help stop cells becoming cancerous by producing proteins that fix damage to our DNA. All of the cells in our body undergo a daily cycle of DNA damage and repair. In a normal day, the DNA in each cell can be damaged between 1,000 and 1,000,000 times! Luckily, we've evolved very efficient ways to either repair the DNA, or destroy the 'broken' cells.

The BRCA genes are an important part of this repair process, so any faults reduce our ability to repair this daily onslaught of DNA damage. This means that mistakes can start to build up in the DNA, which increases the chances of the cell becoming cancerous.

If the BRCA genes are 'breast cancer genes', do BRCA mutations only affect women?

No. Both men and women can inherit a 'faulty' BRCA1 or 2 gene from either their mother or father.

In women, having a mutation in either BRCA1 or BRCA2 is linked to an increased risk of developing breast or ovarian cancer, and a BRCA2 mutation is thought to confer the bigger risk. Men with BRCA1 or 2 mutations are also at increased risk of developing male breast cancer, although this is still much lower than for women and very rare.

Do BRCA 1 and BRCA2 mutations cause prostate cancer?

We don't yet know of any one gene, or group of genes, that can identify all men with, or at high risk of, prostate cancer - this is one of the major goals Prostate Cancer UK is working towards.

There are a number of locations within the DNA that increase a man's risk of developing prostate cancer when they contain mistakes (known as genetic variants). 

We know that some of these 'risk' locations are within the BRCA1 and 2 genes.  However, mutations in BRCA1 and 2 are only found in 0.44% and 1.2% prostate cancer cases respectively. So, while the risk of prostate cancer is increased for men with these mutations, the majority of prostate cancer cases are not linked to BRCA1 or BRCA2 mutations.

If I have a BRCA1 or 2 mutation, will I get prostate cancer?

Having a BRCA1 or BRCA2 mutation does give you an increased risk of getting prostate cancer but it doesn't mean you will definitely get it.

You have two copies of every gene, so if you have a BRCA1 or 2 mutation, it means that one copy of the gene is faulty, but the other one still works perfectly.  In this case, enough protein is produced by the 'perfect' copy of the gene for everything to function as normal. However, if anything happens to the working copy of the gene, that's when DNA damage repair would be affected.  

One study suggests that a man with a BRCA1 mutation is 3.4 times more likely to develop prostate cancer by age 65 than a man without this mutation. This is 8.6 times more likely for a man with a BRCA2 mutation.

If I have a BRCA1 or 2 mutation, should I have regular PSA tests?

You can read about the pros and cons of the PSA test on our website.

The IMPACT clinical trial is happening at the moment, and is investigating whether using the PSA test to screen for prostate cancer would be good for men with a BRCA1 or 2 mutation. It's also testing how BRCA mutations affect the predicted outcome of a man's prostate cancer. The results of this trial are expected in 2017. Early results suggest that regular PSA testing may be beneficial for men with BRCA mutations, but we will need to wait for the final results before we can say for sure.

Is there any evidence that BRCA1 or 2 mutations affect prostate cancer prognosis?

A recent study looked at the effect of BRCA1 and 2 mutations on prostate cancer prognosis (the predicted outcome of the disease). This study looked at men with prostate cancer, and compared those with a BRCA1 or 2 mutation and those without. The scientists found that prostate cancer in men with a BRCA1 or 2 mutation was more likely to be aggressive and to spread beyond the prostate. 

The researchers suggest that this could mean that men who are known to have a BRCA1 or 2 mutation when they are diagnosed with prostate cancer should be treated as high-risk patients immediately. However, before they can confirm these results and make a more definite recommendation, they need to wait for results of the IMPACT study.

Can I be tested for BRCA 1 and 2 mutations?

Men with a strong family history of breast, ovarian or prostate cancer, or who have a family member with a BRCA mutation can be referred for genetic testing on the NHS, but this isn't available everywhere in the UK. There are also private clinics that don't require a GP referral. 

Genetic testing should always be accompanied by specialist counselling to help you understand the possible outcomes of the test, what the results will mean for you and your family, and how you will cope with the information the test reveals.

At the moment there's not enough evidence to say whether or not being tested for BRCA1 or 2 mutations should be done, even in men with a family history of cancer. If you have a family history of cancer and are concerned about your cancer risk, you can discuss this with your GP.

Read more about risk and prostate cancer

comments powered by Disqus